1. Field of the Invention
The present invention relates to a human tumor suppressor gene, a polypeptide coded for thereby and a gene analysis method wherein the above-mentioned gene is used. Thus, they are usable in the field of medicines.
2. Description of the Related Art
It has been known for a long time that gene mutation in cells plays an important role in the onset of cancer. Recent advances in genetic engineering have made it possible to amplify specific DNAs and to analyze gene mutation in cancer cells and thus contributed to the remarkable development in the field of studies on cancer.
Analysis and identification of oncogenes, which are thought to participate in the cancerization of cells and the abnormal proliferation of cancer cells, are now in progress and the number of the oncogenes thus clarified so far amounts to several score. On the other hand, tumor suppressor genes having a reverse function have been the focus of intense research interest in these several years. Examples of the tumor suppressor genes which have been found so far include Rb gene of retinoblastoma [Friend, S. H., et al., Proc. Natl. Acad. Sci. USA., 84, 9095 (1987)], p53 gene [Lane, D. P., et al., Nature, 278, 261 (1979)] and APC gene [Kenneth, W. K., et al., Science, 253, 661 (1991)] of colon cancer and WT1 gene of Wilms' tumor [Call, K. M., et al., Cell, 60, 509 (1990)]. In the case of the p53 gene, it is known that this mutation gene has been handed down over generations as a germ-line in ceratin family lines ["Li-Fraumeni syndrome"; Makin, D., et al., Science, 250, 1233 (1990); and Srivastava, S., et al., Nature, 348, 747 (1990)]. However, it is considered that there are many more unidentified tumor suppressor genes.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disease characterized by the development of hyperplasia or neoplasm in the endocrine organs such as accessory thyroid, islets of Langerhans in the pancreas and pituitary gland [Brandi, M. L., et. al., Endocr. Rev. 8, 391 (1987)]. It is assumed by linkage studies that a genetic defect exists in the long arm of chromosome 11 (11q). Also there is known a region which is deleted with high frequency on chromosome 11q in MEN 1-associated tumors. Based on these facts, it is considered that a tumor suppressor gene exists in this region.
Accordingly, it is now the focus of world-wide interest of physicians and researches to isolate this tumor suppressor gene, to clarify its role in the disease and to clarify its biological function. Thus it has been urgently required to isolate the tumor suppressor gene in this region.
It is an object of the present invention to provide a novel tumor suppressor gene, a transformant transformed by a plasmid having, integrated therein, the full structure or part of the tumor suppressor gene, a polypeptide which is coded for by the tumor suppressor gene, an antibody against the polypeptide and methods for studying, examining, diagnosing and medically treating cancer with the use of them.